Razzetti Roberta, Bergamaschi Marco, Villetti Gino, Bolzoni Piertonino, Civelli Maurizio, Berti Ferruccio, Rossoni Giuseppe
Department of Pharmacology, Chiesi Farmaceutici S.p.A., Via Palermo 26/A, 43100 Parma, Italy.
Pharmacol Res. 2007 May;55(5):426-32. doi: 10.1016/j.phrs.2007.01.018. Epub 2007 Feb 2.
These studies were designed to assess the pharmacodynamic interaction between formoterol and beclomethasone dipropionate (BDP) in controlling the bronchoconstriction and inflammatory response induced by various challenges in guinea-pigs and rats. In anaesthetised guinea-pigs, superfusion of the formoterol/BDP combination into the tracheal lumen had significantly more effect than the single components in antagonising the bronchoconstricting and inflammatory responses to acetylcholine or ovalbumin in a standard model of airway hyper-responsiveness. After ovalbumin challenge, the combination completely protected animals from death at doses lower than those effective when given separately. The combination, at doses ineffective individually, even counteracted the development of lung oedema induced by sephadex in the rat. Finally, in tracheal strips from ovalbumin-sensitised guinea-pigs pre-treatment with BDP (30 mg kg(-1) i.m.) completely reversed the rightward shift of the formoterol dose-response curve due to beta(2)-receptor desensitisation. In conclusion, these results indicate that formoterol and BDP together induce a favourable pharmacodynamic interaction which can be considered more than additive, at least in these experimental settings.
这些研究旨在评估福莫特罗与二丙酸倍氯米松(BDP)在控制豚鼠和大鼠因各种刺激引起的支气管收缩和炎症反应中的药效学相互作用。在麻醉的豚鼠中,在气道高反应性标准模型中,将福莫特罗/BDP组合灌注到气管腔内,在拮抗对乙酰胆碱或卵清蛋白的支气管收缩和炎症反应方面,其效果明显优于单一成分。卵清蛋白激发后,该组合在低于单独给药有效剂量时就能完全保护动物免于死亡。该组合在单独使用无效的剂量下,甚至能抵消葡聚糖诱导的大鼠肺水肿的发展。最后,在卵清蛋白致敏的豚鼠的气管条中,BDP(30 mg kg(-1) 肌肉注射)预处理完全逆转了由于β(2)受体脱敏导致的福莫特罗剂量反应曲线右移。总之,这些结果表明,福莫特罗和BDP共同诱导了一种有利的药效学相互作用,至少在这些实验环境中,这种相互作用可被认为大于相加作用。